Fetal life malnutrition was not reflected in the relative abundances of adiponectin and leptin mRNAs in adipose tissue in male mink kits at 9.5 weeks of age.

BACKGROUND: Malnutrition in fetal life and during suckling have in some animal studies resulted in adaptive changes related to the fat and glucose metabolism, which in the long term might predispose the offspring for metabolic disorders such as obesity later in life. The objective was to study the effect of fetal life malnutrition in male mink on the gene expression of leptin and adiponectin in different adipose tissue sites. RESULTS: Thirty-two male mink, strict carnivore species, exposed to low (FL) or adequate (FA) protein provision the last 16.3 ± 1.8 days of fetal life and randomly assigned to a low (LP) or adequate (AP) protein diet from 7 to 9.5 weeks of age were used. Adipose tissues (subcutaneous, perirenal and mesenteric) were analyzed using qPCR. Fetal life or post-weaning protein provision did not affect the relative abundances of leptin and adiponectin mRNAs in adipose tissue at 9.5 weeks of age. Relative abundances of leptin and adiponectin mRNAs were different between adipose tissue sites and were significantly higher in subcutaneous than in perirenal and mesenteric tissues. CONCLUSION: Fetal life protein malnutrition in male mink, did not result in adaptive changes in the gene expression of leptin and adiponectin mRNAs in adipose tissue at 9.5 weeks of age as found in rodents. However, both leptin and adiponectin mRNAs were significantly differently expressed between tissue sites.

Long-term effects of foetal undernutrition on intermediary metabolism in growing lambs.

The objective of this study was to investigate the effects of foetal undernutrition on the metabolism in growing lambs. Seven-month-old lambs whose mothers had been fed either restrictively (RN; n = 14) or adequately (AN; n = 6) in late gestation were fasted for three days. One hour before fasting and after 48 h and 72 h fasting, changes in plasma concentrations of metabolites, i.e. glucose, nonesterified fatty acids (NEFA), 3-beta-hydroxybutyrate (BOHB) and urea as well as hormones, i.e. insulin, the insulin-like growth factor (IGF-I) and leptin, were determined. Blood glucose, NEFA, urea, insulin, IGF-I and leptin were not different between the two groups of lambs. Unexpectedly, at the end of the 3 d fasting, in spite of lower NEFA concentration (1.6 +/- 0.03 vs. 1.9 +/- 0.05 mM in Groups RN and AN, respectively), the BOHB concentration in RN lambs (0.94 +/- 0.02 mM) was significantly higher than that in AN lambs (0.78 +/- 0.04 mM). This higher rate of BOHB production might be interpreted as perturbations in ketone body metabolism potentially induced by undernutrition during foetal life. However, more investigations are necessary to clarify this interrelationship.

Prenatal induced chronic dietary hypothyroidism delays but does not block adult-type Leydig cell development.

Transient hypothyroidism induced by propyl-2-thiouracyl blocks postpartum Leydig cell development. In the present study, the effects of chronic hypothyroidism on the formation of this adult-type Leydig cell population were investigated, using a more physiological approach. Before mating, dams were put on a diet consisting of an iodide-poor feed supplemented with a low dose of perchlorate and, with their offspring, were kept on this diet until death. In the pups at day 12 postpartum, plasma thyroid-stimulating hormone levels were increased by 20-fold, whereas thyroxine and free tri-iodothyronine levels were severely depressed, confirming a hypothyroid condition. Adult-type progenitor Leydig cell formation and proliferation were reduced by 40-60% on days 16 and 28 postpartum. This was followed by increased Leydig cell proliferation at later ages, suggesting a possible slower developmental onset of the adult-type Leydig cell population under hypothyroid conditions. Testosterone levels were increased 2- to 10-fold in the hypothyroid animals between days 21 and 42 postpartum compared with the age-matched controls. Combined with the decreased presence of 5alpha-reductase, this implicates a lower production capacity of 5alpha-reduced androgens. In 84-day-old rats, after correction for body weight-to-testis weight ratio, plasma insulin-like factor-3 levels were 35% lower in the hypothyroid animals, suggestive of a reduced Leydig cell population. This is confirmed by a 37% reduction in the Sertoli cell-to-Leydig cell ratio in hypothyroid rats. In conclusion, we show that dietary-induced hypothyroidism delays but, unlike propyl-2-thiouracyl, does not block the development of the adult-type Leydig cell population.

Impact of abnormal nutrition during pregnancy on the offspring hormone resistance.

OBJECTIVE: To investigate the impact of abnormal nutrition during pregnancy on the insulin and leptin resistance of adult offsprings. METHODS: The model of abnormal nutrition during pregnancy was established, and these rats were fed whole-course low-protein or high-nutrition. After natural childbirth, the birth weight of each newborn rat was measured. According to the determining birth weights, the newborn rats were assigned into the small for gestational age (SGA) and large for gestational age (LGA) groups as well as the healthy control group, respectively. There was a total of 36 randomly selected rats in each group. The levels of insulin and leptin and the insulin sensitivity index (ISI) were determined by enzymelinked immunosorbent assay 4 and 12 weeks post birth, respectively. RESULTS: In the low-protein group, the birth weight was significantly lower than in the control group (p<0.01) and 68.97% of the newborn rats were SGA; in the high-energy group, the birth weight of the newborn rats was significantly larger than in the control group (p<0.01), and 37.98% of the newborn were LGA. The body weights (BW) of the SGA 4 weeks post birth had no significant difference from that of the controls, while the perirenal fat weight (FW) and the FW/BW ratio were significantly larger than those of the controls (p<0.01 and p<0.05, respectively); however, the FW/BW of the LGA had no significant difference from that of the controls. Twelve weeks after birth, the BW of both SGA and LGA rats increased significantly compared to the controls (p<0.05 and p<0.01, respectively), and the FW/BW ratios of both were significantly larger than that of the controls (p<0.01). For the SGA rats 4 weeks post birth, the insulin and leptin level increased significantly (both p<0.05), while the ISI decreased significantly (p<0.05), with the occurrence of insulin resistance. For both SGA and LGA 12 weeks post birth, the insulin and leptin level significantly increased (both p<0.01). CONCLUSION: Abnormal nutrition during pregnancy could lead to abnormal birth weight, and both low and high birth weight could cause abdominal obesity as well as insulin and leptin resistance in adulthood, although through different mechanisms.

Effect of undernutrition in foetal life on energy expenditure during gestation in ewes.

The long-term effect of early life undernutrition on late gestation energy expenditure (EEgest) was investigated in sheep. Ewes were fed either adequate (100%) or restricted (60%) energy and protein during late foetal life as well as during last trimester of gestation later in life, resulting in three groups: Adequate-Adequate (AA, n = 5), Adequate-Restricted (AR, n = 5) and Restricted-Restricted (RR, n = 5). At two weeks pre-partum, EEgest were calculated from respiratory gaseous exchange and nitrogen excreted in urine and further it was partitioned to energy expenditure for conceptus development (EEconceptus) and homeorhetic adaptations in maternal metabolism (EEhomeorhetic). Late gestational energy and protein restriction reduced the EEgest in the AR ewes (4.1 MJ x d(-1)) but not in the RR ewes (5.2 MJ x d(-1)) compared with the AA ewes (6.8 MJ x d(-1)). Based on conceptus-weight, no significant difference was found in EEhomeorhetic among the groups; 172, 175 and 169 kJ/kg x d(-1) in AA, AR and RR ewes, respectively. However, EEconceptus was significantly lower in AR (135 kJ/kg x d(-1)) in comparison with AA (298 kJ/kg x d(-1)) and RR (252 kJ/kg x d(-1)) ewes. In conclusion, exposure nutrient restriction in early life impairs the ability of ewes to respond to nutritional restriction in terms of energy expenditure of gestation.

Baggs ewes adapt to maternal undernutrition and maintain conceptus growth by maintaining fetal plasma concentrations of amino acids.

Adequate delivery of AA is essential for normal fetal growth and development. Recently, we reported that when ewes from the University of Wyoming flock (farm flock with adequate nutrition) were fed 50% (nutrient-restricted) or 100% (control-fed) of the NRC-recommended nutrient requirements between d 28 and 78 of gestation, fetal weights as well as concentrations of most AA in maternal and fetal blood were substantially reduced in nutrient-restricted vs. control-fed pregnancies. The current study utilized Baggs ewes, which were selected under a markedly different production system (range flock with limited nutrition), to test the hypothesis that adaptation of ewes to nutritional and environmental changes may alter placental efficiency and conceptus nutrient availability in the face of maternal nutrient restriction. Baggs ewes received 50 or 100% of the NRC nutrient requirements between d 28 and 78 of pregnancy. On d 78, maternal uterine arterial and fetal umbilical venous blood samples were obtained, and the ewes were euthanized. Amino acids and their metabolites (ammonia, urea, and polyamines) in plasma were analyzed using enzymatic and HPLC methods. The results showed that maternal plasma concentrations of 9 AA (Asp, Ile, Leu, Lys, Orn, Phe, Thr, Trp, and Val) as well as maternal and fetal plasma concentrations of ammonia and urea were reduced (P < 0.05) in nutrient-restricted compared with control-fed Baggs ewes. However, fetal plasma concentrations of all AA and polyamines did not differ (P = 0.842) between the 2 groups of ewes. Collectively, these findings suggest that Baggs ewes, by adapting to the harsh conditions and limited nutrition under which they were selected, were able to maintain fetal concentrations of AA in the face of a maternal nutrient restriction through augmenting placental efficiency.

The effects of acute nutrient restriction in the mid-gestational ewe on maternal and fetal nutrient status, the expression of placental growth factors and fetal growth.

This study explores the hypothesis that acute under-nutrition in mid-gestation reduces maternal and fetal nutrient status and affects the expression of specific regulators of placental growth and function. Welsh Mountain ewes were fed a concentrate diet plus wheat straw to provide 100% of their maintenance requirements. The concentrate ration of nutrient restricted (NR) ewes was reduced from day (d) 83 of gestation and withdrawn from d85 to d90. At d90, half the ewes (NR m = 7, control n = 8) were euthanased. The remainder (NR n = 9, control n = 9) were fed their maintenance diet until slaughter at d135. Maternal plasma insulin and IGF-I concentrations decreased during nutrient restriction and NEFA concentrations increased. Fetal IGF-I and insulin concentrations were unaltered by maternal diet. Placental VEGF mRNA expression was reduced at d90 (P < 0.05). IGFBP-3 and IGFBP-2 mRNA expression was reduced at d90 (P < 0.05) and d135 (P < 0.05), respectively. Placental weight was significantly lower in NR ewes at d90 (P < 0.05) and the distribution of placentomes shifted towards the everted phenotype at d135 (P < 0.05). Reduced thoracic girth and uterine fluid volume at d90 (P < 0.05) and decreased fetal lung weight at d90 (P < 0.05) and d135 (P < 0.05) suggest spatial limitation of lung expansion. In summary, acute NR in mid-gestation reduced anabolic drive and mobilised lipid stores in the maternal compartment, whilst fetal nutrient status was maintained. This was accompanied by changes in placental VEGF and IGFBP expression. The growth of the fetal lung appears to have been compromised and this may have adverse consequences for subsequent neonatal respiratory function.